Humanized Germ-Free Mice for Investigating the Intervention Effect of Commensal Microbiome on Cancer Immunotherapy

A growing body of evidence has demonstrated that the commensal microbiome is deeply involved in the host immune response, accounting for significantly divergent clinical outcomes among cancer patients receiving immunotherapy. Therefore, precise screening and evaluating of functional bacterial strains as novel targets for cancer immunotherapy have attracted great enthusiasm from both academia and industry, which calls for the construction and application of advanced animal models to support translational research in this field. Significant progress has been made to elucidate the intervention effect of commensal microbiome on immunotherapy based on animal experiments. Especially, correlation between gut microbiota and host response to immunotherapy has been continuously discovered in a variety of cancer types, laying the foundation for causality establishment and mechanism research. In oncology research, it is particularly not uncommon to see that a promising preclinical result fails to translate into clinical success. The use of conventional murine models in immunotherapy-associated microbiome research is very likely to bring discredit on the preclinical findings. We emphasize the value of germ-free (GF) mice and humanized mice as advanced models in this field. Integrating rederivation and humanization to generate humanized GF mice as preclinical models would make it possible to clarify the role of specific bacterial strains in immunotherapy as well as obtain preclinical findings that are more predictive for humans, leading to novel microbiome-based strategies for cancer immunotherapy. Antioxid. Redox Signal. 37, 1291-1302.